• BMB Reports
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• v.42 no.7
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• pp.421-426
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• 2009

Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.

• BMB Reports
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• v.48 no.7
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• pp.367-368
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• 2015

It has long been thought that glucocorticoid receptor (GR) functions as a DNA-binding transcription factor in response to its ligand (a glucocorticoid) and thus regulates various cellular and physiological processes. It is also known that GR can bind not only to DNA but also to mRNA; this observation points to the possible role of GR in mRNA metabolism. Recent data revealed a molecular mechanism by which binding of GR to target mRNA elicits rapid mRNA degradation. GR binds to specific RNA sequences regardless of the presence of a ligand. In the presence of a ligand, however, the mRNA-associated GR can recruit PNRC2 and UPF1, both of which are specific factors involved in nonsense-mediated mRNA decay (NMD). PNRC2 then recruits the decapping complex, consequently promoting mRNA degradation. This mode of mRNA decay is termed "GR-mediated mRNA decay" (GMD). Further research demonstrated that GMD plays a critical role in chemotaxis of immune cells by targeting CCL2 mRNA. All these observations provide molecular insights into a previously unappreciated function of GR in posttranscriptional regulation of gene expression. [BMB Reports 2015; 48(7): 367-368]

• Molecules and Cells
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• v.39 no.8
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• pp.631-638
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• 2016

Glutathione peroxidase 3 (GPx3), an antioxidant enzyme, acts as a modulator of redox signaling, has immunomodulatory function, and catalyzes the detoxification of reactive oxygen species (ROS). GPx3 has been identified as a tumor suppressor in many cancers. Although hyper-methylation of the GPx3 promoter has been shown to down-regulate its expression, other mechanisms by which GPx3 expression is regulated have not been reported. The aim of this study was to further elucidate the mechanisms of GPx3 regulation. GPx3 gene analysis predicted the presence of ten glucocorticoid response elements (GREs) on the GPx3 gene. This result prompted us to investigate whether GPx3 expression is regulated by the glucocorticoid receptor (GR), which is implicated in tumor response to chemotherapy. The corticosteroid dexamethasone (Dex) was used to examine the possible relationship between GR and GPx3 expression. Dex significantly induced GPx3 expression in H1299, H1650, and H1975 cell lines, which exhibit low levels of GPx3 expression under normal conditions. The results of EMSA and ChIP-PCR suggest that GR binds directly to GRE 6 and 7, both of which are located near the GPx3 promoter. Assessment of GPx3 transcription efficiency using a luciferase reporter system showed that blocking formation of the GR-GRE complexes reduced luciferase activity by 7-8-fold. Suppression of GR expression by siRNA transfection also induced down-regulation of GPx3. These data indicate that GPx3 expression can be regulated independently via epigenetic or GR-mediated mechanisms in lung cancer cells, and suggest that GPx3 could potentiate glucocorticoid (GC)-mediated anti-infla-mmatory signaling in lung cancer cells.

• Korean Journal of Ichthyology
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• v.20 no.3
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• pp.149-155
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• 2008

The effects of noise stress response on hematological parameters (hemoglobin, hematocrit and MCHC) and plasma parameters (cortisol, glucose and albumin) in Korean rockfish (Sebastes schlegeli), a very important commercial marine fish in Korea, were investigated. These parameters were analyzed on fish exposed to an explosion of noise. There were no significant differences or trends in hematological parameters (hematocrit; control $29.7{\pm}4.8%$, experiment 32.0 35.5%; hemoglobin; control $6.5{\pm}0.7g/dL$, experiment 6.2 7.8 g/dL; MCHC; control $19.6{\pm}0.6g/dL$, experiment 19.9~22.2 g/dL). However, plasma cortisol and glucose exhibited significant differences from start to finish and displayed the following patterns (cortisol; control $180.7{\pm}35.4ng/mL$, experiment 247.0 444.5 ng/mL; glucose; control $32.5{\pm}6.3mg/dL$, experiment 50.5 109.0 mg/dL). In addition, the glucocorticoid receptor (GR) mRNA expression and basal levels of various tissues (eye, gills, liver, intestine, skin and gonads) were investigated for the first time in this marine fish. When the Korean rockfish was exposed to explosive noise stress, the GR mRNA was expressed more in the gonads than in other tissues tested and was elevated significantly from two and four times in the liver and gills, respectively, after noise exposure.

• Proceedings of the Ginseng society Conference
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• 2008.05a
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• pp.76-76
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• 2008

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2005.10a
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• pp.133-133
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• 2005

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2005.10a
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• pp.133-133
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• 2005

• BMB Reports
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• v.49 no.3
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• pp.167-172
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• 2016

Kaiso is a Pox Virus and Zinc Finger (POZ-ZF) transcription factor with bi-modal DNA-binding specificity. Here, we demonstrated that Kaiso expression is inversely correlated with glucocorticoid receptor (GR) expression in breast carcinomas. Knockdown of Kaiso increased GR expression, while overexpression of Kaiso inhibited GR expression in breast cancer cells. Furthermore, Kaiso repressed GR proximal promoter-reporter activity in a dose-dependent manner. Remarkably, ChIP experiments demonstrated that endogenous Kaiso was associated with the GR promoter sequence in a methylation-dependent manner. Since glucocorticoids inhibit chemotherapyinduced apoptosis and have been widely used as a co-treatment of patients with breast cancer, we assessed the role of Kasio in GR-mediated anti-apoptotic effects. We found that overexpression of Kaiso attenuated the anti-apoptotic effects of glucocorticoids in breast cancer cells. Our findings suggest that GR is a putative target gene of Kaiso and suggest Kaiso to be a potential therapeutic target in GC-combination chemotherapy in breast cancer.

• BMB Reports
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• v.50 no.10
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• pp.522-527
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• 2017

A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ~70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which might be important for its activity. We carried out heteronuclear multi-dimensional NMR experiments on hGR tau1c in a more physiological aqueous buffer solution and found that it forms three helices that are ~30% pre-populated. Since pre-populated helices in several TADs were shown to be key elements for transcriptional activity, the three pre-formed helices in hGR tau1c delineated in this study should be critical determinants of the transcriptional activity of hGR. The presence of pre-structured helices in hGR tau1c strongly suggests that the existence of pre-structured motifs in target-unbound TADs is a very broad phenomenon.

• Bulletin of the Korean Chemical Society
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• v.26 no.8
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• pp.1209-1213
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• 2005

Nuclear membrane is one of the main barriers in intracellular delivery of genetic materials. The previous report showed that glucocorticoid receptor dilated the nuclear pore to 60 nm in the presence of a ligand. It was also suggested that the transport of genetic material to nucleus might be facilitated by glucocorticoid. In this study, the effect of glucocorticoid preincubation in the polymeric gene delivery was investigated. The cells were preincubated with dexamethasone, a potent glucocorticoid, and transfection assays were performed with polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer. As a result, the transfection efficiency of PEI or PAMAM to the cells in the presence of dexamethasone was enhanced, compared to the cells without dexamethasone. This effect was not observed in the cells preincubated with cholesterol. The polymer/DNA complex was stable in the presence of dexamethasone. In addition, the cytotoxicities of the polymeric carriers to the cells were observed in the presence of dexamethasone. In conclusion, dexamethasone enhances the transfection efficiency of polymeric carriers and may be useful in the development of polymeric gene carriers.